Faculty Advisor

Dr. Michael Parra

Start Date

April 2021

End Date

April 2021

Description

In eukaryotic cells, DNA is wrapped around histone proteins to form the basic repeating unit of chromatin, the nucleosome core particle. Most nucleosomes consist of two copies each of histones: H2A and H2B in a heterodimer and histones H3 and H4 in a heterotetramer. Because of their intimate association with DNA, histones regulate all DNA-templated processes such as transcription, DNA replication, and DNA damage response and repair. Several studies have illustrated the importance of a small portion of the histone H2A amino terminal domain which regulates global transcription. This domain is responsible for the repression of ~4% of the yeast genome. This domain, termed the histone H2A Repression (H.A.R.) domain, consists of a small, conserved portion (amino acids 16-20) of histone H2A. The H.A.R. domain has also been shown to be an important regulator of DNA damage response and repair. In this study, we find that deletion of the H.A.R. domain leads to a defect in cell proliferation. Indeed, deletion of the domain leads to a marked sensitivity to hydroxyurea, indicating a defect in either DNA damage response or DNA replication machinery. Intriguingly, we find that the RNR2 gene (which regulates the transition of nucleoside triphosphates into deoxynucleotide triphosphates) is down regulated in these mutants. Finally, we find that deletion of the H.A.R. domain leads to an abnormal number of cells that show an apparent delay in the transition out of S-phase in the cell cycle. Taken together, these data points illustrate the importance of this domain in proper progression through the cell cycle.

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Apr 27th, 12:00 AM Apr 27th, 12:00 AM

Interrogating the Functions of the Histone H2A Repression Domain in Relation to Cell-Cycle Progression in Saccharomyces cerevisiae

In eukaryotic cells, DNA is wrapped around histone proteins to form the basic repeating unit of chromatin, the nucleosome core particle. Most nucleosomes consist of two copies each of histones: H2A and H2B in a heterodimer and histones H3 and H4 in a heterotetramer. Because of their intimate association with DNA, histones regulate all DNA-templated processes such as transcription, DNA replication, and DNA damage response and repair. Several studies have illustrated the importance of a small portion of the histone H2A amino terminal domain which regulates global transcription. This domain is responsible for the repression of ~4% of the yeast genome. This domain, termed the histone H2A Repression (H.A.R.) domain, consists of a small, conserved portion (amino acids 16-20) of histone H2A. The H.A.R. domain has also been shown to be an important regulator of DNA damage response and repair. In this study, we find that deletion of the H.A.R. domain leads to a defect in cell proliferation. Indeed, deletion of the domain leads to a marked sensitivity to hydroxyurea, indicating a defect in either DNA damage response or DNA replication machinery. Intriguingly, we find that the RNR2 gene (which regulates the transition of nucleoside triphosphates into deoxynucleotide triphosphates) is down regulated in these mutants. Finally, we find that deletion of the H.A.R. domain leads to an abnormal number of cells that show an apparent delay in the transition out of S-phase in the cell cycle. Taken together, these data points illustrate the importance of this domain in proper progression through the cell cycle.

 

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